Adenylate Kinase 4
In 2014, we identified adenylate kinase 4 (AK4) as an important regulator of cellular bioenergetics. Expression of this mitochondrial matrix-localized adenylate kinase appears to significantly impact overall cellular ATP levels as well as the activation status of the AMPK energy-sensing signaling pathway. Our current efforts are focused on determining 1) how AK4 expression impacts ATP levels, 2) how AMPK signaling is regulated by AK4, and 3) what the functional consequences of AK4-regulated ATP levels and AMPK signaling are from a cell biology perspective.
This work on AK4 biology is funded by National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) Grant 1R15GM123382.
This work on AK4 biology is funded by National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) Grant 1R15GM123382.
Leigh Syndrome
Leigh Syndrome is a disease caused by an inability of mitochondria to produce enough energy to support cellular life. This disease primarily affects children, with symptoms initially presenting between a few months to two years of age. Because Leigh Syndrome is severe and has no cure, the majority of patients die in childhood. The objective of this project is to develop cell models that replicate the genetic mutations affecting the electron transport chain which cause this disease, and verify the cellular symptoms of Leigh Syndrome in these cell models. An additional objective of this project is to determine if suppression of AK4 expression or activity in the context of the Leigh Syndrome cell models restores cellular energy to normal levels and enhances the ability of these cells to survive.
This work on Leigh Syndrome cell models is funded by The California State University Program for Education and Research in Biotechnology (CSUPERB) New Investigator Grant.
This work on Leigh Syndrome cell models is funded by The California State University Program for Education and Research in Biotechnology (CSUPERB) New Investigator Grant.
Redox Homeostasis & Cancer Biology
Mitochondria are integral for cellular maintenance of homeostasis in response to cellular metabolic and oxidative stresses. In this capacity, mitochondria provide cells with critical metabolic flexibility and significant capacity to buffer cellular redox status. Cancer cells are commonly exposed to high levels of oxidative stress due to their rapid proliferation and altered metabolic requirements. Therefore, cancer cells must find ways to counteract this oxidative stress. It is currently understood that both normal and altered mitochondrial function are essential for malignant tumors to maintain their oncogenic potential. While some mitochondrial functions which support cancer biology are known, the organelle as a whole remains to be systematically characterized for its role in cancer biology. The goal of our research is to determine whether the mitochondrial proteins responsible for maintaining cellular homeostasis in response to various stresses are necessary for cancer cell survival. In collaboration with the Filipp laboratory at UC Merced, we are also interrogating all cellular redox-regulators (both mitochondrial and non-mitochondrial regulators) in melanoma cells.